Advances in the Chemistry of Chiral Lithium Amides

Harrison‐Marchand, Anne; Maddaluno, Jacques

doi:10.1002/9783527667512.ch10

Cited by 14 publications

(7 citation statements)

References 143 publications

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“…Chiral lithium amides have been extensively used in asymmetric synthesis, as powerful bases for the deprotonation of prochiral compounds and as chiral auxiliaries. − The high synthetic value of these reagents has prompted many studies into their structural chemistry in attempts to better understand their complex and often highly selective behavior. ,− …”

Section: Introductionmentioning

confidence: 99%

Loss of Chirality through Facile Lewis Base Mediated Aza-enolate Formation in Na and K (S)-N-(α-Methylbenzyl)methallylamides

et al. 2016

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Metalation of (S)-N-(α-methylbenzyl)methallylamine with nBuM (M = Li, Na, or K) in hexane leads to the allylic metal amides [(S)-PhCH(CH3)N(CH2C{CH3}CHLi)Li]6, 1, [(S)-PhCH(CH3)N(CH2C{CH3}CH2)Na] n , and [(S)-PhCH(CH3)N(CH2C{CH3}CH2)K] n , respectively. The addition of any Lewis base (here THF, TMEDA, or PMDETA) to the Na and K amides promotes rapid anion rearrangement to the aza-enolate complexes [PhC(CH2)N(CH2CH{CH3}2)Na]∞, 2, [PhC(CH2)N(CH2CH{CH3}2)Na·TMEDA] n , 3, [PhC(CH2)N(CH2CH{CH3}2)Na·PMDETA] n , 4, and [PhC(CH2)N(CH2CH{CH3}2)K] n , 5, resulting in loss of chirality. In contrast, the addition of benzene leads exclusively to the 1-aza-allyl complexes [(S)-PhCH(CH3)N(CHC{CH3}2)Na] n , 6, and [(S)-PhCH(CH3)N(CHC{CH3}2)K] n , 7, both of which are not observed in the presence of Lewis donors. Doping a benzene solution of 7 with THF gives the first observation of reorganization to the intermediate 2-aza-allyl anion. All seven complexes have been characterized by NMR spectroscopy, with complexes 1 and 2 also being characterized by single-crystal X-ray diffraction. Rearrangement to the aza-enolates 2 and 3 is unprecedented under the conditions employed.

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Section: Introductionmentioning

confidence: 99%

Loss of Chirality through Facile Lewis Base Mediated Aza-enolate Formation in Na and K (S)-N-(α-Methylbenzyl)methallylamides

et al. 2016

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“…Enantiopure C 2 -symmetric secondary amines are important constructional pieces of chiral phosphoramidite ligands [13] as well as the precursors of chiral lithium amides for enantioselective deprotonations and conjugate addition reactions. [14] Such amines are most commonly synthesized through the reduction of imines and the reductive amination of aromatic ketones through enantio-induction with chiral amine sources. [15] In 2016 Wakchaure and List reported a novel two-step catalytic enantioselective reductive condensation reaction of aromatic N-H imines obtained from abundant aromatic ketone sources for the construction of C 2 -symmetric amines by using a disulfonimide Brønsted acid catalyst.…”

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confidence: 99%

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

Gao

Huang

et al. 2021

Angewandte Chemie

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Asymmetric reductive amination (ARA) is one of the most promising methods for the synthesis of chiral amines. Herein we report our efforts on merging two ARA reactions into a single-step transformation. Catalyzed by a complex formed from iridium and a steric hindered phosphoramidite, readily available and inexpensive aromatic ketones initially undergo the first ARA with ammonium acetate to afford primary amines, which serve as the amine sources for the second ARA, and finally provide the enantiopure C 2 -symmetric secondary amine products. The developed process competently enables the successive coupling of inorganic and organic nitrogen sources with ketones in the same reaction system. The Brønsted acid additive plays multiple roles in this procedure: it accelerates the formation of imine intermediates, minimizes the inhibitory effect of N-containing species on the iridium catalyst, and reduces the primary amine side products.Scheme 1. Nitrogen sources for asymmetric reductive amination.

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“…The enantioselective alkylation of enolates is a fundamental and broadly utilized transformation in stereoselective organic synthesis. Chiral auxiliary-based methods for alkylation of carboxylic acids in which the auxiliary is covalently bound have gained widespread application in both industrial and academic settings. , Chiral lithium amides, which form mixed aggregates with organolithium and other organometallic reagents, offer an alternative approach to asymmetric alkylation of enolates. , Within the context of these complex aggregates, chiral lithium amides in effect function as noncovalent, or traceless, chiral auxiliaries. Formed in situ, they provide a chiral environment enabling asymmetric transformations.…”

mentioning

confidence: 99%

Direct Enantioselective and Regioselective Alkylation of β,γ-Unsaturated Carboxylic Acids with Chiral Lithium Amides as Traceless Auxiliaries

Miao

Wang

et al. 2019

Org. Lett.

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Advances in the Chemistry of Chiral Lithium Amides

Cited by 14 publications

References 143 publications

Loss of Chirality through Facile Lewis Base Mediated Aza-enolate Formation in Na and K (S)-N-(α-Methylbenzyl)methallylamides

Loss of Chirality through Facile Lewis Base Mediated Aza-enolate Formation in Na and K (S)-N-(α-Methylbenzyl)methallylamides

An Iridium Catalytic System Compatible with Inorganic and Organic Nitrogen Sources for Dual Asymmetric Reductive Amination Reactions

Direct Enantioselective and Regioselective Alkylation of β,γ-Unsaturated Carboxylic Acids with Chiral Lithium Amides as Traceless Auxiliaries

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